Chiral Cavity Research Articles

Nitrogen-Oxidized Tröger's Base Macrocyclic Arenes: Unprecedented Enantioselective Recognition in Water.

Achieving high enantioselectivity with synthetic receptors, particularly in water, remains a significant challenge despite the success seen in natural biological systems. In this study, we introduce a facile synthesis of Tröger's base (TB)-containing macrocyclic arenes (TBn), where TB units are linked via methylene bridges, providing the macrocycles with a rigid framework. Oxidation of enantiopure TBn yields corresponding chiral nitrogen oxides (TBnNO) with excellent water solubility, attributed to the high polarity of the N-O bond, surpassing the pH limitations of traditional ion-functionalized approaches. Remarkably, TBnNO exhibits exceptional enantioselective recognition toward a wide range of chiral guests in aqueous solution, achieving enantioselectivities as high as 41.0. The underlying mechanism involves a combination of hydrophobic interactions and steric effects caused by rigid chiral cavities. These findings highlight the potential of nitrogen-oxidized macrocycles as a transformative tool for supramolecular application in water.

Nitrogen‐Oxidized Tröger's Base Macrocyclic Arenes: Unprecedented Enantioselective Recognition in Water

Achieving high enantioselectivity with synthetic receptors, particularly in water, remains a significant challenge despite the success seen in natural biological systems. In this study, we introduce a facile synthesis of Tröger's base (TB)‐containing macrocyclic arenes (TBn), where TB units are linked via methylene bridges, providing the macrocycles with a rigid framework. Oxidation of enantiopure TBn yields corresponding chiral nitrogen oxides (TBnNO) with excellent water solubility, attributed to the high polarity of the N‐O bond, surpassing the pH limitations of traditional ion‐functionalized approaches. Remarkably, TBnNO exhibits exceptional enantioselective recognition toward a wide range of chiral guests in aqueous solution, achieving enantioselectivities as high as 41.0. The underlying mechanism involves a combination of hydrophobic interactions and steric effects caused by rigid chiral cavities. These findings highlight the potential of nitrogen‐oxidized macrocycles as a transformative tool for supramolecular application in water.

Stacking Transformation-Triggered Circularly Polarized Luminescence Reversion in γ-Cyclodextrins-Pyrene Co-Assembly.

Considerable attention has been directed towards cyclodextrins (CDs) in the creation of co-assembled CPL-active materials, owing to their intrinsic chiral host cavities and synergistic host-guest interactions. However, achieving reversed CPL emission regulation with single-handedness CDs moiety poses a significant challenge. In this study, we have devised a series of γ-CD-based host-guest complexes comprising dual pyrene imidazolium derivatives with multiple linkers, which exhibit reversed circularly polarized emission. We have uncovered that the transformation of excimer stacking within γ-CD/pyrene complexes contributes to the inverted CPL emissions originating from a single-handed chiral host. This research elucidates the phenomenon of (+)- and (-)-circularly polarized excimer emission (CPEE) within γ-CD, arising from right- and left-handed stacking conformations, respectively.

Engineering topology in graphene with chiral cavities

Engineering topology in graphene with chiral cavities

Cooperative Binding and Chirogenesis in an Expanded Perylene Bisimide Cyclophane.

The encapsulation of more than one guest molecule into a synthetic cavity is a highly desirable yet a highly challenging task to achieve for neutral supramolecular hosts in organic media. Herein, we report a neutral perylene bisimide cyclophane, which has a tailored chiral cavity with an interchromophoric distance of 11.2 Å, capable of binding two aromatic guests in a π-stacked fashion. Detailed host-guest binding studies with a series of aromatic guests revealed that the encapsulation of the second guest in this cyclophane is notably more favored than the first one. Accordingly, for the encapsulation of the coronene dimer, a cooperativity factor (α) as high as 485 was observed, which is remarkably high for neutral host-guest systems. Furthermore, a successful chirality transfer, from the chiral host to encapsulated coronenes, resulted in a chiral charge-transfer (CT) complex and the rare observation of circularly polarized emission originating from the CT state for a noncovalent donor-acceptor assembly in solution. The involvement of the CT state also afforded an enhancement in the luminescence dissymmetry factor (glum) value due to its relatively large magnetic transition dipole moment. The 1:2 binding pattern and chirality-transfer were unambiguously verified by single-crystal X-ray diffraction analysis of the host-guest superstructures.

On-demand polarization by a vertical-cavity surface-emitting laser with two tilted sub-wavelength gratings.

We show that each polarization state on the Poincaré sphere (PS) can be accessed on-demand (Poincaré sphere tailoring) by a semiconductor-based vertical-cavity surface-emitting laser (VCSEL) with two tilted sub-wavelength gratings (SWGs). We develop a vectorial Barkhausen criterion that answers the question: what conditions must the cavity fulfill to support a given desired polarization state? Addressing this inquiry leads to a completely different strategy based on the entangled interplay between two tilted SWGs, resulting in an overall chiral cavity, whose features depend on the gratings and their mutual rotation. This leads to the emission of a well-controllable polarization state based on standard technologies used in polarization-stable VCSELs, which paves the way for inspiring several new potential applications.

Carborane-Cluster-Wrapped Copper Cluster with Cyclodextrin-like Cavities for Chiral Recognition.

Chiral atomically precise metal clusters, known for their remarkable chiroptical properties, hold great potential for applications in chirality recognition. However, advancements in this field have been constrained by the limited exploration of host-guest chemistry, involving metal clusters. This study reports the synthesis of a chiral Cu16(C2B10H10S2)8 (denoted as Cu16@CB8, where C2B10H12S2H2 = 9,12-(HS)2-1,2-closo-carborane) cluster by an achiral carboranylthiolate ligand. The chiral R-/S-Cu16@CB8 cluster features chiral cavities reminiscent of cyclodextrins, which are surrounded by carborane clusters, yet they crystallize in a racemate. These cyclodextrin-like cavities demonstrated the specific recognition of amino acids, as indicated by the responsive output of circular dichroism and circularly polarized luminescence signals of Cu16 moieties of the Cu16@CB8 cluster. Notably, a quantitative chiroptical analysis of amino acids in a short time and a concomitant deracemization of Cu16@CB8 were achieved. Density functional tight-binding molecular dynamics simulation and noncovalent interaction analysis further unraveled the great importance of the cavities and binding sites for chiral recognition. Dipeptide, tripeptide, and polypeptide containing the corresponding amino acids (Cys, Arg, or His residues) display the same chiral recognition, showing the generality of this approach. The functional synergy of dual clusters, comprising carborane and metal clusters, is for the first time demonstrated in the Cu16@CB8 cluster, resulting in the valuable quantification of the enantiomeric excess (ee) value of amino acids. This work opens a new avenue for chirality sensors based on chiral metal clusters with unique chiroptical properties and inspires the development of carborane clusters in host-guest chemistry.

Enantioselectivity regulation of antibody against chiral herbicide metolachlor based on interaction at chiral center

Enantioselective antibodies have emerged as great potential biomaterials in the fields of immunoassays and chiral separation. However, cross-reactivity of antibodies to the distomer may severely restrict the application. Comprehending the interaction mechanism between antibodies and enantiomers could be beneficial to produce superior enantioselective antibodies. In this study, a pair of recombinant antibodies (RAbs) against metolachlor enantiomers at chiral carbon (αSS-MET and αSR-MET) were generated and characterized. The αSS-MET-RAb and αSR-MET-RAb showed comparable sensitivity and specificity to the parental monoclonal antibodies by icELISA, with IC50 values of 3.45 and 223.77 ng/mL, respectively. Moreover, the complex structures of RAbs and corresponding eutomer were constructed and analyzed, and site-specific mutagenesis was utilized to verify the reliability of the enantioselective mechanism elucidated. It demonstrated that the strength of the interaction between the chiral center region of eutomer and the antibody was the key factor for the enantioselectivity of antibody. Increasing this interaction could limit the conformational adjustment of the distomer in a specific chiral recognition cavity, thus decreasing the affinity of the antibody to the distomer. This work provided the in-depth analysis of enantioselective mechanism for two RAbs and paved the way to regulate antibody enantioselective performance for immunoassays of chiral compounds.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids

AbstractThe precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep‐cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M−1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

Engineering Flat Bands in Twisted-Bilayer Graphene away from the Magic Angle with Chiral Optical Cavities.

Twisted bilayer graphene (TBG) is a recently discovered two-dimensional superlattice structure which exhibits strongly correlated quantum many-body physics, including strange metallic behavior and unconventional superconductivity. Most of TBG exotic properties are connected to the emergence of a pair of isolated and topological flat electronic bands at the so-called magic angle, θ≈1.05°, which are nevertheless very fragile. In this work, we show that, by employing chiral optical cavities, the topological flat bands can be stabilized away from the magic angle in an interval of approximately 0.8°<θ<1.3°. As highlighted by a simplified theoretical model, time reversal symmetry breaking (TRSB), induced by the chiral nature of the cavity, plays a fundamental role in flattening the isolated bands and gapping out the rest of the spectrum. Additionally, TRSB suppresses the Berry curvature and induces a topological phase transition, with a gap closing at the Γ point, towards a band structure with two isolated flat bands with Chern number equal to 0. The efficiency of the cavity is discussed as a function of the twisting angle, the light-matter coupling and the optical cavity characteristic frequency. Our results demonstrate the possibility of engineering flat bands in TBG using optical devices, extending the onset of strongly correlated topological electronic phases in moiré superlattices to a wider range in the twisting angle.

An innovative combination of molecular modeling and green analysis approaches for the enantioseparation and quantitation of certain CNS acting drugs using HPLC

Enantioseparation of three antidepressants from a group called serotonin and noradrenaline reuptake inhibitor (SNRIS) was investigated on chiral stationary phases; Lux-Amylose-2 (amylose tris-(5-chloro-2-methylphenylcarbamate) and Chiral Pak(R) IE Amylose tris (3,5-dichlorophenyl carbamate) in normal phase mode. The mobile phase composed of n-hexane: ethanol diethylamine (96:4:0.2 by volume) has successfully resolved three pairs of enantiomers of the antidepressant drugs namely, fluoxetine, venlafaxine, and mirtazapine on Chiral Pak(R) IE Amylose tris (3,5-dichlorophenyl carbamate) stationary phase. The mobile phase was pumped at a flow rate of 1 ml/min with column temperature 20 °C using a UV detector at 270.0 nm. Sharp and well-resolved peaks for the enantiomers of each cited drug were obtained with retention times 6.47, 7.04 for fluoxetine, 9.33, 9.67 for venlafaxine and 19.27, 25.36 for mirtazapine. Good linearity and accuracy values were obtained over a concentration range of 1000–5000 μg/ml for each analyte. A better comprehension of the interaction and chiral recognition between analyte enantiomers and chiral stationary phase was achieved by conducting a molecular docking simulation on the two chiral stationary phase cavities for the three pairs of enantiomers. According to the results, hydrogen bond interactions and π-π interactions were the main types of interaction involved in the chiral recognition on Chiral Pak(R) IE Amylose tris (3,5-dichlorophenyl carbamate) stationary phase, which provided an optimum chiral enantioseparation of the three drugs. The greenness assessment of the novel applied technique was performed and was found to be with acceptable greenness profile. The proposed method could be implemented in quality control laboratory and in wastewater analysis for the cited drugs.

Self-assembly of two pairs of homochiral M2L4 coordination capsules with varied confined space using Tröger's base ligands

Chiral coordination molecular cages/capsules with discrete nanoconfined chiral cavities demonstrate significant potential applications across various fields. In this study, we utilized Tröger's base as the building block to design and synthesize two pairs of enantiopure ligands. These ligands were then self-assembled with Pd(II) ions through chiral self-sorting coordination, resulting in the formation of two pairs of homochiral M2L4-type coordination molecular capsules. Notably, due to differences in the substitution positions on the Tröger's base, these two pairs of enantiomeric coordination molecular capsules exhibited distinct levels of cavity closures, cavity sizes, and host-guest recognition properties. This research offers valuable insights into the construction of novel chiral molecular capsules and the regulation of confined cavities.

Photon condensation, Van Vleck paramagnetism, and chiral cavities

We introduce a gauge-invariant model of planar, square molecules coupled to a quantized spatially varying cavity electromagnetic vector potential Â(r). Specifically, we choose a temporally cavity hosting a uniform magnetic field B̂, as this is the simplest instance in which a transverse spatially varying Â(r) is at play. We show that when the molecules are in the Van Vleck paramagnetic regime, an equilibrium quantum phase transition to a photon condensate state occurs. Published by the American Physical Society 2024

Chiral Bis-phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination.

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.

Spatial arrangements of cyclodextrin host-guest complexes in solution studied by 13C NMR and molecular modelling.

13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host-guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the crystallization of host-guest complexes and their crystallographic analysis.

Chiral Truxene-Based Self-Assembled Cages: Triple Interlocking and Supramolecular Chirogenesis.

Incorporating chiral elements in host-guest systems currently attracts much attention because of the major impact such structures may have in a wide range of applications, from pharmaceuticals to materials science and beyond. Moreover, the development of multi-responsive and -functional systems is highly desirable since they offer numerous benefits. In this context, we describe herein the construction of a metal-driven self-assembled cage that associates a chiral truxene-based ligand and a bis-ruthenium complex. The maximum separation between both facing chiral units in the assembly is fixed by the intermetallic distance within the lateral bis-ruthenium complex (8.4 Å). The resulting chiral cavity was shown to encapsulate polyaromatic guest molecules, but also to afford a chiral triply interlocked [2]catenane structure. The formation of the latter occurs at high concentration, while its disassembly could be achieved by the addition of a planar achiral molecule. Interestingly the planar achiral molecule exhibits induced circular dichroism signature when trapped within the chiral cavity, thus demonstrating the ability of the cage to induce supramolecular chirogenesis.

Chiral Truxene‐Based Self‐Assembled Cages: Triple Interlocking and Supramolecular Chirogenesis

AbstractIncorporating chiral elements in host–guest systems currently attracts much attention because of the major impact such structures may have in a wide range of applications, from pharmaceuticals to materials science and beyond. Moreover, the development of multi‐responsive and ‐functional systems is highly desirable since they offer numerous benefits. In this context, we describe herein the construction of a metal‐driven self‐assembled cage that associates a chiral truxene‐based ligand and a bis‐ruthenium complex. The maximum separation between both facing chiral units in the assembly is fixed by the intermetallic distance within the lateral bis‐ruthenium complex (8.4 Å). The resulting chiral cavity was shown to encapsulate polyaromatic guest molecules, but also to afford a chiral triply interlocked [2]catenane structure. The formation of the latter occurs at high concentration, while its disassembly could be achieved by the addition of a planar achiral molecule. Interestingly the planar achiral molecule exhibits induced circular dichroism signature when trapped within the chiral cavity, thus demonstrating the ability of the cage to induce supramolecular chirogenesis.

Enantioselective Recognition of Functional Organic Molecules in Water by Biomimetic Macrocyclic Hosts.

Enantioselective recognition of functional organic molecules in water is routine in nature but remains a formidable challenge for synthetic hosts. Here, we reported two pairs of chiral naphthotubes with chiral centers located in the neighborhood of the inward-directing amide groups. These naphthotubes, with a chiral twisted cavity, show highly enantioselective recognition in water to a wide scope of organic molecules (90 chiral guests). The highest enantioselectivity of 34 was achieved with neotame. Small differences between all of the noncovalent interactions shielded in the hydrophobic cavity were revealed to be responsible for the enantioselective recognition in water, which is different from the traditional views. Moreover, these hosts can differentiate the analogues of aspartame using fluorescence spectroscopy. These chiral naphthotubes have made unprecedented achievements in enantioselective recognition, providing the basis for their applications in chiral analysis and separations.

Introducing chirality in porous organic cages through solid-state interactions.

Molecular cages contain an internal cavity designed to encapsulate other molecules, resulting in applications in molecular separation, gas storage, and catalysis. Introducing chirality in cage molecules can improve the selective separation of chiral molecules and add new functionalities due to the realisation of chiral photophysical properties. It has recently been shown that solid-state supramolecular interactions between achiral cages can result in the formation of chiral cavities. Here, we develop a computational technique to predict when achiral cages form chiral cavities in the solid-state through the combination of atomistic calculations and coarse-grained modelling to predict the crystalline phase behaviour. Our focus is on the achiral cage B11, which contains rotatable arene rings on the vertices of the cage that can form propeller-like orientations, inducing a chiral cavity. We show that by using dimer pair calculations, we can inform coarse-grained models to predict the packing of the cage. Our results reveal how the supramolecular interactions drive chirality in the achiral cages without the need for a chiral guest. These findings are a first step towards understanding how we can design chirality through supramolecular interactions by using abstract coarse-grained models to inform design principles for targeted solid-state phase behaviour.